Sodium hypochlorite (bleach) is commonly used as an irrigant during dental proce­dures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo­chlorite has never been implicated as a cause of an acute kidney injury (AKI). In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis.

Sodium hypochlorite, the active ingredient in bleach, is an extremely useful chemical that has been used since the 18 th century as a disinfectant. In medicine, it has been employed as an antiseptic in the treatment of gangrene, burns and other wounds. [1] In the circulation, sodium hypochlorite combines with water to generate hypochlorus acid, conferring potent antibacterial and antifungal properties. Hypo­chlorus acid generates superoxide radicals, resulting in oxidative injury and bacterial/cell death. [2],[3]

When used topically in concentrations ran­ging from 0.5-5.25% solution, its safety and efficacy as an antiseptic has been well esta­blished in animal and human subjects, and its application in dentistry is commonplace. [1] Applied topically, there is no published evi­dence of systemic toxicity or severe local reaction. [1]

At stronger concentrations approximating household bleach (3-5.25%), interstitial inocu­lation of sodium hypochlorite can be highly toxic. Sodium hypochlorite produces imme­diate hemolysis of red blood cells in vitro when introduced in isotonic solutions, which is consistent with a strong oxidizing effect on cell membranes. [3] Many other studies have de­monstrated dose-dependent toxicity associated with sodium hypochlorite when there is direct injection into tissue. [4] Sodium hypochlorite is potentially lethal if a significant amount is absorbed systemically; the dose required to be lethal in 50% of the tested animals (LD 50 ) was 33.3 mg/kg when administered intravenously to rats. [1]

During endodontic procedures, there is a risk of sodium hypochlorite toxicity because it is a preferred irrigation solution for sterilizing the root-canal system. [4] During dental procedures such as in this report, injection of sodium hypochlorite beyond the apical foramen can result in direct interstitial deposition. In the literature, reports of sodium hypochlorite toxi­city are associated with immediate evidence of tissue injury; facial edema, hemorrhage, ecchymosis, severe pain, paresthesias of the face and residual hyperesthesia have been reported. [5] However, there are no prior reports describing the systemic effect of exposure to sodium hypochlorite leading to renal tubular injury and AKI as described in the present case.

Case Report

A 60-year-old man underwent a dental proce­dure to fill dental caries during which he inadvertently received an injection of 1.75 mL of sodium hypochlorite, instead of lidocaine, into his right infraorbital tissue. Immediately following the injection, local facial swelling, hemorrhage into tissue and necrosis along the gum line was apparent. He was directed by the dentist to go to the emergency department (ED) of the nearest hospital. There, he was evaluated and given IV methylprednisolone, diphenhydramine and amoxicillin. No fever or hypotension was documented. After a period of observation, he was discharged from the ED with a 5-day oral steroid taper and 7-day course of amoxicillin (500 mg qid) with instructions to follow-up with his doctor.

Four days after his exposure, he visited his primary care physician with complaints of per­sistent facial edema and ecchymosis [Figure 1] as well as patchy ecchymoses distant to the in­jection site, including the submandibular area, anterior neck and sternum [Figure 2]. He also complained of dark urine - he denied dysuria, urinary frequency or decrease in urine volume. A complete blood count showed a mildly ele­vated white blood cell count of 12.1 k/uL (reference range 4.50-11.00 k/uL), although he neither reported any subjective fever nor was he febrile at presentation. Laboratory studies four days after the exposure revealed serum creatinine of 0.8 mg/dL, but urinalysis showed hematuria with >200 red blood cells per high-powered field and normal levels of urine myo­globin (<1 mg/L), trace proteinuria and urine microscopy (performed by clinical lab) showed granular casts. Given the urinary results, he was subsequently referred for the nephrolo­gical evaluation. Ten days after exposure, he underwent evaluation by a nephrologist, who confirmed the persistence of 1-3 granular casts per high-powered field on the microscopic evaluation of the spun urine sediment. On follow-up 20 days after the initial exposure, his physical exam revealed resolution of the facial edema and improvement in ecchymoses. Repeat urinalysis and examination of urine sediment showed no granular casts, suggesting renal recovery from tubular insult.

Figure 1: Photograph of the patient's facial ecchymoses after injection of sodium hypochlorite into the right infraorbital tissue.

There have been a number of reports in the medical literature describing toxic injury to the kidney from systemic exposure to chemicals: bilateral ureteral obstruction following renal papillary necrosis after ingestion of hydro­chloric acid and Rodine; [6] hemolytic uremic syndrome after ingestion of monochloroacetic acid; [7] hemolysis and acute kidney injury (AKI) from potassium dichromate; [8] acute tubular necrosis after ingestion of ethylene glycol, [9] and others. However, to the best of our know­ledge, sodium hypochlorite has never been implicated as an etiology of AKI, making this report unique.

The diagnosis of AKI secondary to renal tubular injury was established by observation of granular casts by a trained nephrologist. Examination of the spun urine sediment is a highly reliable tool for the diagnosis of AKI and acute tubular necrosis (ATN), specifi­cally. [10] Perazella et al showed that urine microscopy is a valuable and accurate pre­dictor of ATN. [11] A simple scoring system based on the number of renal tubule epithetlium cells and granular casts seen in the urine sediment can predict the likelihood of ATN versus pre-renal AKI. The findings in this case correlate to a likelihood ratio of 2.7 for ATN compared with pre-renal AKI based on the appearance of urine sediment. In patients with an initial clinical diagnosis of ATN, any granular casts in the urine resulted in a positive predictive value of 100% for final diagnosis of ATN. In patients with low pre-test probability of ATN, the lack of granular casts or renal tubular epithelial cells had a negative pre­dictive value of 91% for final diagnosis of non-ATNAKI. [11]

It is interesting that despite clear evidence of renal tubular injury and AKI, based on urine sediment, the serum creatinine did not increase significantly. It is conceivable that in the ensuing four days following the exposure that the patient's creatinine could have increased and then declined by the time it was first tested. It is also possible that the injury was insufficient to raise serum creatinine. Serum creatinine is a rough marker for kidney injury, and often diffuse injury is required to raise serum values of creatinine in patients with normal renal function. Non-oliguric forms of ATN have been reported in nephrotoxic poi­soning and can follow a more benign clinical course. [9]

In this case, accidental injection of sodium hypochlorite into the orofacial tissues led to systemic ecchymoses and AKI in the form of renal tubular injury, leading to mild ATN. This was most likely caused by reactive chlorine compounds that produced oxidative damage to the renal tubular epithelium. Similar to the mechanism of action of the myeloperoxidase reaction in neutrophils, these compounds hydrolyze and neutralize amino acids and oxidize epithelial cell membranes leading to cell death. [2] The evidence for the role of oxidative damage in ATN is well established, whether it is from ischemic changes or nephrotoxins, as in this case. [12],[13] It is important to note that the evaluation of the patient's hematuria displayed a high concentration (>200 per high-power fields) of red blood cells and a normal con­centration of myoglobin. This demonstrates that the patient's renal tubular injury was a result of direct epithelial damage rather than hemolysis or rhabdomyolysis with pigmenturia. An alternative mechanism for renal injury that we considered was transient bacteremia caused by the release of dental flora in the systemic circulation. Although this remains a possibility, at no point did the patient develop fever or hypotension despite a mild leukocyto­sis after the exposure to the insult, which is most likely the result of a systemic inflam­matory response to the damaged facial tissue. The distant ecchymoses are evidence of the systemic spread of sodium hypochlorite after the injection, which we speculate resulted in tissue injury to the kidney.

Accidental injection of sodium hypochlorite has been described several times in the lite­rature, and it is important that clinicians be aware of all the potential adverse events rela­ted to this exposure. We speculate that direct tubular epithelial injury occurred as a result of sodium hypochlorite exposure. This is the first report demonstrating that ATN is an important diagnosis to consider after systemic sodium hypochlorite exposure during a dental proce­dure.

Disclosure Statement

Conflict of interest: None. Also, the authors disclose no financial interest with regard to this paper.